Paper spray has been developed for direct mass spectrometry analysis of complex samples. It has been implemented for sample analysis on commercial lab-scale mass spectrometers as well as miniature mass spectrometers. Since its development, a set of unique advantages have been shown for paper spray through a variety of applications. For example, it is easy to implement paper spray. A triangle paper substrate with a sharp tip is used as the sample substrate and the liquid sample is deposited to form a dried sample spot, such as a dried blood spot (DBS). Direct sampling ionization is performed by wetting the substrate with a solvent and applying a high voltage of about 4000 V. The solvent elutes the analytes from the sample spot and a spray ionization is generated at the tip of the substrate to produce the analyte ions for mass spectrometry analysis. Paper spray is also suitable for design of disposable sample cartridges, which is important for implementing ambient ionization for clinical, especially point-of-care (POC) analysis using mass spectrometry. A commercial aftermarket paper spray source using disposable sample cartridge has been developed and used in clinical applications.
However, there are certain limitations to paper spray. Paper spray has not interfaced well with mass spectrometers that utilize a curtain gas (e.g., Sciex instruments). Paper spray has also had issues being interfaced with miniature mass spectrometers. Also, the sharp tip of a paper spray probe directly influences the performance of the probe and mass production processes for fabricating the paper substrates, such as die cutting, have inconsistency issues for making a sharp tip from the paper.